Abstract | BACKGROUND:
Antimicrobial peptides ( AMP) are an important defense mechanism of the innate immune system and can modulate the course of various diseases. However, their significance during liver pathogenesis is currently not well defined. METHODS: RESULTS: First, serum samples from patients with chronic liver diseases were investigated. Therefore, significantly enhanced levels for LL-37, hBD2, and complement C5a were detected, all of which comprise antimicrobial properties. Next, CRAMP-knockout ( CRAMP-KO) mice were investigated, to better define a functional role of LL-37/ CRAMP in animal models of liver diseases. MCD feeding and bile-duct ligation of CRAMP-KO mice resulted in an enhanced degree of liver injury during the early treatment phase. MCD feeding in CRAMP-KO mice led to stronger intrahepatic fat accumulation and significantly enhanced matrix remodeling, whereas BDL caused more extensive liver necrosis. At the late 28 days time point, MCD-fed CRAMP-KO mice displayed a higher intrahepatic fat load. Long-term changes in bile-duct-ligated mice included higher collagen content as a sign of enhanced fibrosis progression if CRAMP was absent. CONCLUSION: The study shows a clear correlation of antimicrobial peptide serum levels in patients with chronic liver diseases. Furthermore, we were able to demonstrate protective functions of LL-37/ CRAMP in two independent mouse models of chronic liver injury.
|
Authors | Svenja Wertenbruch, Hannah Drescher, Vera Grossarth, Daniela Kroy, Arne Giebeler, Stephanie Erschfeld, Daniel Heinrichs, Oliver Soehnlein, Christian Trautwein, Lars-Ove Brandenburg, Konrad Streetz |
Journal | Digestion
(Digestion)
Vol. 91
Issue 4
Pg. 307-17
( 2015)
ISSN: 1421-9867 [Electronic] Switzerland |
PMID | 25998843
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Antimicrobial Cationic Peptides
- Cathelicidins
- DEFB4A protein, human
- Immunologic Factors
- beta-Defensins
- Complement C5a
- Methionine
|
Topics |
- Animals
- Antimicrobial Cationic Peptides
- Bile Ducts
(surgery)
- Cathelicidins
(blood, immunology)
- Choline Deficiency
- Complement C5a
(analysis)
- Diet Therapy
(adverse effects, methods)
- Humans
- Immunologic Factors
(blood)
- Ligation
(adverse effects)
- Liver
(immunology, injuries)
- Liver Diseases
(blood, immunology)
- Methionine
(deficiency)
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- beta-Defensins
(blood)
|